The Major Cellular Sterol Regulatory Pathway Is Required for Andes Virus Infection

English version České info

The Bunyaviridae comprise a large family of RNA viruses with worldwide distribution and includes the pathogenic New World hantavirus, Andes virus (ANDV). Host factors needed for hantavirus entry remain largely enigmatic and therapeutics are unavailable. To identify cellular requirements for ANDV infection, we performed two parallel genetic screens. Analysis of a large library of insertionally mutagenized human haploid cells and a siRNA genomic screen converged on components (SREBP-2, SCAP, S1P and S2P) of the sterol regulatory pathway as critically important for infection by ANDV. The significance of this pathway was confirmed using functionally deficient cells, TALEN-mediated gene disruption, RNA interference and pharmacologic inhibition. Disruption of sterol regulatory complex function impaired ANDV internalization without affecting virus binding. Pharmacologic manipulation of cholesterol levels demonstrated that ANDV entry is sensitive to changes in cellular cholesterol and raises the possibility that clinically approved regulators of sterol synthesis may prove useful for combating ANDV infection.

Vyšlo v časopise: The Major Cellular Sterol Regulatory Pathway Is Required for Andes Virus Infection. PLoS Pathog 10(2): e32767. doi:10.1371/journal.ppat.1003911
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1003911

Souhrn

Zdroje

1. MacneilA, NicholST, SpiropoulouCF (2011) Hantavirus pulmonary syndrome. Virus Res 162 : 138–147.

2. MacNeilA, KsiazekTG, RollinPE (2011) Hantavirus pulmonary syndrome, United States, 1993–2009. Emerg Infect Dis 17 : 1195–1201.

3. RasmusonJ, AnderssonC, NorrmanE, HaneyM, EvanderM, et al. (2011) Time to revise the paradigm of hantavirus syndromes? Hantavirus pulmonary syndrome caused by European hantavirus. Eur J Clin Microbiol Infect Dis 30 : 685–690.

4. CalisherCH, MillsJN, RootJJ, DotyJB, BeatyBJ (2011) The relative abundance of deer mice with antibody to Sin Nombre virus corresponds to the occurrence of hantavirus pulmonary syndrome in nearby humans. Vector Borne Zoonotic Dis 11 : 577–582.

5. HjertqvistM, KleinSL, AhlmC, KlingstromJ (2010) Mortality rate patterns for hemorrhagic fever with renal syndrome caused by Puumala virus. Emerg Infect Dis 16 : 1584–1586.

6. ArikawaJ, SchmaljohnAL, DalrympleJM, SchmaljohnCS (1989) Characterization of Hantaan virus envelope glycoprotein antigenic determinants defined by monoclonal antibodies. J Gen Virol 70 (Pt 3) 615–624.

7. LoberC, AnheierB, LindowS, KlenkHD, FeldmannH (2001) The Hantaan virus glycoprotein precursor is cleaved at the conserved pentapeptide WAASA. Virology 289 : 224–229.

8. DeydeVM, RizvanovAA, ChaseJ, OttesonEW, St JeorSC (2005) Interactions and trafficking of Andes and Sin Nombre Hantavirus glycoproteins G1 and G2. Virology 331 : 307–315.

9. HigaMM, PetersenJ, HooperJ, DomsRW (2012) Efficient production of Hantaan and Puumala pseudovirions for viral tropism and neutralization studies. Virology 423 : 134–142.

10. JinM, ParkJ, LeeS, ParkB, ShinJ, et al. (2002) Hantaan virus enters cells by clathrin-dependent receptor-mediated endocytosis. Virology 294 : 60–69.

11. BrownKS, SafronetzD, MarziA, EbiharaH, FeldmannH (2011) Vesicular stomatitis virus-based vaccine protects hamsters against lethal challenge with Andes virus. J Virol 85 : 12781–12791.

12. CaretteJE, RaabenM, WongAC, HerbertAS, ObernostererG, et al. (2011) Ebola virus entry requires the cholesterol transporter Niemann-Pick C1. Nature 477 : 340–343.

13. RayN, WhidbyJ, StewartS, HooperJW, Bertolotti-CiarletA (2010) Study of Andes virus entry and neutralization using a pseudovirion system. J Virol Methods 163 : 416–423.

14. HuaX, NohturfftA, GoldsteinJL, BrownMS (1996) Sterol resistance in CHO cells traced to point mutation in SREBP cleavage-activating protein. Cell 87 : 415–426.

15. RawsonRB, ChengD, BrownMS, GoldsteinJL (1998) Isolation of cholesterol-requiring mutant Chinese hamster ovary cells with defects in cleavage of sterol regulatory element-binding proteins at site 1. J Biol Chem 273 : 28261–28269.

16. SakaiJ, DuncanEA, RawsonRB, HuaX, BrownMS, et al. (1996) Sterol-regulated release of SREBP-2 from cell membranes requires two sequential cleavages, one within a transmembrane segment. Cell 85 : 1037–1046.

17. ReyonD, KhayterC, ReganMR, JoungJK, SanderJD (2012) Engineering designer transcription activator-like effector nucleases (TALENs) by REAL or REAL-Fast assembly. Curr Protoc Mol Biol Chapter 12: Unit 12 15.

18. HawkinsJL, RobbinsMD, WarrenLC, XiaD, PetrasSF, et al. (2008) Pharmacologic inhibition of site 1 protease activity inhibits sterol regulatory element-binding protein processing and reduces lipogenic enzyme gene expression and lipid synthesis in cultured cells and experimental animals. J Pharmacol Exp Ther 326 : 801–808.

19. EngelS, HegerT, ManciniR, HerzogR, KartenbeckJ, et al. (2011) Role of Endosomes in Simian Virus 40 Entry and Infection. Journal of Virology 85 : 4198–4211.

20. LuYE, CasseseT, KielianM (1999) The Cholesterol Requirement for Sindbis Virus Entry and Exit and Characterization of a Spike Protein Region Involved in Cholesterol Dependence. Journal of Virology 73 : 4272–4278.

21. FinkelshteinD, WermanA, NovickD, BarakS, RubinsteinM (2013) LDL receptor and its family members serve as the cellular receptors for vesicular stomatitis virus. Proc Natl Acad Sci U S A 110 : 7306–7311.

22. KilsdonkEPC, YanceyPG, StoudtGW, BangerterFW, JohnsonWJ, et al. (1995) Cellular Cholesterol Efflux Mediated by Cyclodextrins. Journal of Biological Chemistry 270 : 17250–17256.

23. MatlinKS, ReggioH, HeleniusA, SimonsK (1981) Infectious entry pathway of influenza virus in a canine kidney cell line. J Cell Biol 91 : 601–613.

24. SakaiT, OhuchiM, ImaiM, MizunoT, KawasakiK, et al. (2006) Dual wavelength imaging allows analysis of membrane fusion of influenza virus inside cells. J Virol 80 : 2013–2018.

25. MercerJ, SchelhaasM, HeleniusA (2010) Virus entry by endocytosis. Annu Rev Biochem 79 : 803–833.

26. CaretteJE, GuimaraesCP, VaradarajanM, ParkAS, WuethrichI, et al. (2009) Haploid genetic screens in human cells identify host factors used by pathogens. Science 326 : 1231–1235.

27. GuimaraesCP, CaretteJE, VaradarajanM, AntosJ, PoppMW, et al. (2011) Identification of host cell factors required for intoxication through use of modified cholera toxin. J Cell Biol 195 : 751–764.

28. PapatheodorouP, CaretteJE, BellGW, SchwanC, GuttenbergG, et al. (2011) Lipolysis-stimulated lipoprotein receptor (LSR) is the host receptor for the binary toxin Clostridium difficile transferase (CDT). Proc Natl Acad Sci U S A 108 : 16422–16427.

29. ReilingJH, ClishCB, CaretteJE, VaradarajanM, BrummelkampTR, et al. (2011) A haploid genetic screen identifies the major facilitator domain containing 2A (MFSD2A) transporter as a key mediator in the response to tunicamycin. Proc Natl Acad Sci U S A 108 : 11756–11765.

30. CaretteJE, GuimaraesCP, WuethrichI, BlomenVA, VaradarajanM, et al. (2011) Global gene disruption in human cells to assign genes to phenotypes by deep sequencing. Nat Biotechnol 29 : 542–546.

31. SchlegelmilchK, MohseniM, KirakO, PruszakJ, RodriguezJR, et al. (2011) Yap1 acts downstream of alpha-catenin to control epidermal proliferation. Cell 144 : 782–795.

32. RosmarinDM, CaretteJE, OliveAJ, StarnbachMN, BrummelkampTR, et al. (2012) Attachment of Chlamydia trachomatis L2 to host cells requires sulfation. Proc Natl Acad Sci U S A 109 : 10059–10064.

33. JaeLT, RaabenM, RiemersmaM, van BeusekomE, BlomenVA, et al. (2013) Deciphering the glycosylome of dystroglycanopathies using haploid screens for lassa virus entry. Science 340 : 479–483.

34. ZhouH, XuM, HuangQ, GatesAT, ZhangXD, et al. (2008) Genome-scale RNAi screen for host factors required for HIV replication. Cell Host Microbe 4 : 495–504.

35. KonigR, ZhouY, EllederD, DiamondTL, BonamyGM, et al. (2008) Global analysis of host-pathogen interactions that regulate early-stage HIV-1 replication. Cell 135 : 49–60.

36. YeungML, HouzetL, YedavalliVS, JeangKT (2009) A genome-wide short hairpin RNA screening of jurkat T-cells for human proteins contributing to productive HIV-1 replication. J Biol Chem 284 : 19463–19473.

37. BushmanFD, MalaniN, FernandesJ, D'OrsoI, CagneyG, et al. (2009) Host cell factors in HIV replication: meta-analysis of genome-wide studies. PLoS Pathog 5: e1000437.

38. DayaM, CervinM, AndersonR (1988) Cholesterol enhances mouse hepatitis virus-mediated cell fusion. Virology 163 : 276–283.

39. VashishthaM, PhalenT, MarquardtMT, RyuJS, NgAC, et al. (1998) A single point mutation controls the cholesterol dependence of Semliki Forest virus entry and exit. J Cell Biol 140 : 91–99.

40. LuYE, CasseseT, KielianM (1999) The cholesterol requirement for sindbis virus entry and exit and characterization of a spike protein region involved in cholesterol dependence. J Virol 73 : 4272–4278.

41. DanthiP, ChowM (2004) Cholesterol removal by methyl-beta-cyclodextrin inhibits poliovirus entry. J Virol 78 : 33–41.

42. PhalenT, KielianM (1991) Cholesterol is required for infection by Semliki Forest virus. J Cell Biol 112 : 615–623.

43. MarquardtMT, PhalenT, KielianM (1993) Cholesterol is required in the exit pathway of Semliki Forest virus. J Cell Biol 123 : 57–65.

44. PelkmansL, KartenbeckJ, HeleniusA (2001) Caveolar endocytosis of simian virus 40 reveals a new two-step vesicular-transport pathway to the ER. Nat Cell Biol 3 : 473–483.

45. PelkmansL, PuntenerD, HeleniusA (2002) Local actin polymerization and dynamin recruitment in SV40-induced internalization of caveolae. Science 296 : 535–539.

46. RodalSK, SkrettingG, GarredO, VilhardtF, van DeursB, et al. (1999) Extraction of cholesterol with methyl-beta-cyclodextrin perturbs formation of clathrin-coated endocytic vesicles. Mol Biol Cell 10 : 961–974.

47. PatelKP, CoyneCB, BergelsonJM (2009) Dynamin -⁠ and lipid raft-dependent entry of decay-accelerating factor (DAF)-binding and non-DAF-binding coxsackieviruses into nonpolarized cells. J Virol 83 : 11064–11077.

48. TannerLB, LeeB (2013) The greasy response to virus infections. Cell Host Microbe 13 : 375–377.

49. Amini-Bavil-OlyaeeS, ChoiYJ, LeeJH, ShiM, HuangIC, et al. (2013) The antiviral effector IFITM3 disrupts intracellular cholesterol homeostasis to block viral entry. Cell Host Microbe 13 : 452–464.

50. MudhasaniR, TranJP, RettererC, RadoshitzkySR, KotaK, et al. (2013) Ifitm-2 and Ifitm-3 but Not Ifitm-1 Restrict Rift Valley Fever Virus. J Virol 87 (15) 8451–64.

51. LiuSY, AliyariR, ChikereK, LiG, MarsdenMD, et al. (2013) Interferon-inducible cholesterol-25-hydroxylase broadly inhibits viral entry by production of 25-hydroxycholesterol. Immunity 38 : 92–105.

52. BlancM, HsiehWY, RobertsonKA, KroppKA, ForsterT, et al. (2013) The transcription factor STAT-1 couples macrophage synthesis of 25-hydroxycholesterol to the interferon antiviral response. Immunity 38 : 106–118.

53. GavrilovskayaIN, BrownEJ, GinsbergMH, MackowER (1999) Cellular Entry of Hantaviruses Which Cause Hemorrhagic Fever with Renal Syndrome is Mediated by Beta3 Integrins. Journal of Virology 73 : 3951–3959.

54. GavrilovskayaIN, ShepleyM, RShaw, GinsbergMH, MackowER (1998) Beta3 integrins mediate the cellular entry of hantaviruses that cause respiratory failure. Proclamations of the National Academy of Sciences 95 : 7074–7079.

55. RaymondT, GorbunovaE, GavrilovskayaIN, MachowER (2005) Pathogenic hantaviruses bind plexin-semaphorin-integrin domains present at the apex of inactive bent alphaV-beta3 integrin conformers. Proclamations of the National Academy of Sciences 102 : 1163–1168.

56. MatthysVS, GorbunovaEE, GavrilovskayaIN, MachowER (2010) Andes Virus Recognition of Human and Syrian Hamster Beta3 Integrins Is Determined by an L33P Substitution in the PSI Domain. Journal of Virology 84 : 352–360.

57. LawsonND, StillmanEA, WhittMA, RoseJK (1995) Recombinant vesicular stomatitis viruses from DNA. Proc Natl Acad Sci U S A 92 : 4477–4481.

58. OginoM, YoshimatsuK, EbiharaH, ArakiK, LeeBH, et al. (2004) Cell fusion activities of Hantaan virus envelope glycoproteins. J Virol 78 : 10776–10782.

59. NorburyCC, MalideD, GibbsJS, BenninkJR, YewdellJW (2002) Visualizing priming of virus-specific CD8+ T cells by infected dendritic cells in vivo. Nat Immunol 3 : 265–271.

60. WangGP, CiuffiA, LeipzigJ, BerryCC, BushmanFD (2007) HIV integration site selection: analysis by massively parallel pyrosequencing reveals association with epigenetic modifications. Genome Res 17 : 1186–1194.

61. CherryS, DoukasT, ArmknechtS, WhelanS, WangH, et al. (2005) Genome-wide RNAi screen reveals a specific sensitivity of IRES-containing RNA viruses to host translation inhibition. Genes Dev 19 : 445–452.

62. LefrancoisL, LylesDS (1982) The interaction of antibody with the major surface glycoprotein of vesicular stomatitis virus. I. Analysis of neutralizing epitopes with monoclonal antibodies. Virology 121 : 157–167.

63. LefrancoisL, LylesDS (1982) The interaction of antibody with the major surface glycoprotein of vesicular stomatitis virus. II. Monoclonal antibodies of nonneutralizing and cross-reactive epitopes of Indiana and New Jersey serotypes. Virology 121 : 168–174.

64. LivakKJ, SchmittgenTD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the ΔΔCT method. Methods 25 : 402–408.

65. DahlemTJ, HoshijimaK, JurynecMJ, GuntherD, StarkerCG, et al. (2012) Simple methods for generating and detecting locus-specific mutations induced with TALENs in the zebrafish genome. PLoS Genet 8: e1002861.

66. GuschinDY, WaiteAJ, KatibahGE, MillerJC, HolmesMC, et al. (2010) A rapid and general assay for monitoring endogenous gene modification. Methods Mol Biol 649 : 247–256.